1. Field of the Invention
The compound, 5-bromopyrimidine, has proven to be a valuable intermediate in the synthesis of several new agricultural products, particularly those which have interesting growth regulator and fungicidal properties, as taught in Belgian Pat. No. 714,003. The importance of these products led to a search for a more facile synthesis of the important intermediate, 5-bromopyrimidine.
2. Description of the Prior Art
In the prior art, Bredereck et al., Chem. Ber. 91, 2832 at 2848 (1958), teach the reaction of pyrimidine hydrochloride with bromine by heating a mixture of the two in an oil bath for about 3 hours at a temperature of about 160.degree.C., to form a solid mass, the reaction product mixture. The temperature of the oil bath was then raised to 250.degree.C., and the 5-bromopyrimidine hydrobromide was sublimed out of the solid reaction product mixture under vacuum. The 5-bromopyrimidine hydrobromide was taken up in sodium bisulfite solution, the solution made alkaline with potassium hydroxide, and extracted with chloroform. The chloroform was distilled to leave behind pure 5-bromopyrimidine.
An alternate approach to the synthesis of 5-bromopyrimidine is also reported by Bredereck et al., Chem. Ber. 95, 803 at 807 and 808 (1962). 2-Bromo-1,1,3,3-tetraethoxypropane was prepared by brominating 1,1,3,3-tetraethoxypropane in carbon tetrachloride. The 2-bromo-1,1,3,3-tetraethoxypropane was then condensed with formamde, in the presence of ammonium formate and water, to give 5-bromopyrimidine.
Yet another method of preparation of 5-bromopyrimidine is described by van der Does, Tetrahedron Letters 22, 2183-2186 (1972), accomplished by bromination of pyrimidine in the gas phase at a temperature of from 220.degree. to 500.degree.C., optimally, 300.degree.C., for a 35-40 percent yield of 5-bromopyrimidine.
The preparation of 4-bromoisoquinoline is taught by Gilman et al., J. Am. Chem. Soc. 69, 1946 (1947). Isoquinoline perbromide hydrobromide was subjected to prolonged heating, yielding a solid mass. Excess aqueous sodium hydroxide solution was added to the solid mass and the liberated 4-bromoisoquinoline was recovered by steam distillation. The crude product was purified by recrystallization from petroleum ether.
The preparation of 5-bromo-4-phenylpyrimidine via a six-step synthetic process is reported by van der Plas, Rec. Trav. Chim. 84, 1101 (1965), who stated that the direct bromination method of Bredereck et al., supra, did not seem suitable for the synthesis of 5-bromo-4-phenylpyrimidine, the phenyl group being vulnerable to the attack of brominating agents.
The preparation of 3-bromoquinoline by the pyrolysis of quinoline hydrobromide perbromide at 180.degree.-200.degree.C. is reported by Eisch, J Org. Chem. 27, 1318 (1962).